Project Abstract Cerebrovascular diseases (CVD) with large-vessel stenosis or occlusion as one of the leading causes of death and disability in all societies, impose enormous social-economic burden worldwide. Quantitative cerebral perfusion mapping is increasingly utilized at different stages of clinical workup, including evaluation of the microcirculation of affected vascular territories acutely and beyond, guiding medical vs. interventional therapy, prognostication, and longitudinal follow-ups. PET with [15O]-water is considered as the reference standard for cerebral blood flow (CBF) measurement but is less accessible than CT and MRI for clinical evaluation of vascular diseases. The mainstay of clinical MR perfusion mapping is dynamic susceptibility contrast perfusion weighted imaging (DSC-PWI). For patients with large vessel occlusive diseases, accurate CBF quantification requires a deconvolution technique that is insensitive to long arterial transit delay. The ability of arterial spin labeling (ASL) to estimate absolute CBF without relying on exogenous contrast agents provides a non-invasive, more quantitative, and often preferred alternative to DSC-PWI in the non-acute setting, particularly when there is contraindication to Gadolinium contrast. ASL methods typically apply spatially selective labeling modules at supplying arteries distant from imaging volumes. The standardized ASL technique recommended for clinical applications is the single-delay pseudo-continuous ASL (PCASL) method, which is known to be sensitive to delayed transit time. Newly developed velocity-selective arterial spin labeling (VSASL) can minimize the time- delay sensitivity but suffers low signal-to-noise ratio due to the use of saturation-based labeling modules. We recently developed Fourier transform based velocity-selective inversion (FT-VSI) pulse trains that allows higher sensitivity to perfusion signal and better immunity to gradient imperfection. The purpose of this study is first to further refine VSASL techniques in healthy people (Aim 1); then to assess the reproducibility and sensitivity of VSASL in healthy people (Aim 2); and finally to evaluate and validate VSASL in patients with large- vessel steno-occlusive CVD (Aim 3). The proposed VSASL techniques are expected to show clinical values not only for the brain, but also for the rest of the body, and especially benefit children, pregnant women, and patients with diabetes or impaired kidney function.